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Congo red and thioflavin-T analogs detect Abeta oligomers
Authors:Maezawa Izumi  Hong Hyun-Seok  Liu Ruiwu  Wu Chun-Yi  Cheng R Holland  Kung Mei-Ping  Kung Hank F  Lam Kit S  Oddo Salvatore  Laferla Frank M  Jin Lee-Way
Institution:M.I.N.D. Institute and Department of Pathology, University of California Davis, Sacramento, California, USA;
Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, Sacramento, California, USA;
Department of Molecular and Cellular Biology, University of California Davis, Davis, California, USA;
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA;
Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, USA
Abstract:Several small molecule ligands for amyloid-β (Aβ) fibrils deposited in brain have been developed to facilitate radiological diagnosis of Alzheimer's disease (AD). Recently, the build-up of Aβ oligomers (AβO) in brain has been recognized as an additional hallmark of AD and may play a more significant role in early stages. Evidence suggests that quantitative assessment of AβO would provide a more accurate index of therapeutic effect of drug trials. Therefore, there is an urgent need to develop methods for efficient identification as well as structural analysis of AβO. We found that some well established amyloid ligands, analogs of Congo red and thioflavin-T (ThT), bind AβO with high affinity and detect AβO in vitro and in vivo . Binding studies revealed the presence of binding sites for Congo red- and thioflavin-T-analogs on AβO. Furthermore, these ligands can be used for imaging intracellular AβO in living cells and animals and as positive contrast agent for ultrastructural imaging of AβO, two applications useful for structural analysis of AβO in cells. We propose that by improving the binding affinity of current ligands, in vivo imaging of AβO is feasible by a 'signal subtraction' procedure. This approach may facilitate the identification of individuals with early AD.
Keywords:Alzheimer  amyloid  imaging  ligand  oligomer  small molecule
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